A major emphasis of this project has been to define the relationship of exogenous hormones to subsequent cancer risk. Using a similar approach as had been used to examine the effects of exogenous hormones on breast cancer risk, analyses within the context of a large screening program showed an association of menopausal hormone use with the risk of ovarian cancer. These analyses showed risk to increase with years of use of hormones, particularly when the preparation used was unopposed estrogens. Relationships with endometrial cancer are being pursued with additional follow-up data. Also of interest is the relationship of breast implants to subsequent cancer risk. Breast cancer risk has been of concern, given that breast implants can interfere with the mammographic visualization of lesions. However, in a large retrospective study that we conducted, we found no evidence for an alteration in breast cancer risk. These patients also generally did not experience alterations in other cancer sites, although elevations were observed in the risk of lung and brain cancers, the explanation for which remains unclear. In a mortality analysis, implant patients had signficantly elevated risks of death from suicide, but other causes of death were similar to the general population. Currently underway are analyses of risk of connective tissue diseases related to breast implants. In addition, we are continuing to follow the cohort for mortality to determine whether previously observed patterns persist. A retrospective cohort study is also being conducted to examine the effects on cancer risk of different causes of infertility and of different associated therapies. This study involves detailed abstraction of medical records of patients diagnosed as long ago as the 1960's and administration of questionnaires to obtained updated health information. A strength of the study is the detailed information collected on causes of infertility. This hasl enabled analyses related to how specific endocrinologic abnormalities relate to cancer risk. In addition, analyses have been undertaken to determine whether there is a link with ovulation-stimulating drugs. In a separate investigation, conducted in collaboration with investigators in Denmark, cancer risk among children conceived following use of ovulation-stimulating drugs has been assessed. Preliminary analyses show no alteration in childhood cancer risk. A number of medical conditions have been suggested as predisposing to the risk of breast, endometrial and ovarian cancers, but most of these studies have relied on patients reports of these prior conditions. To obtain more precise information on the nature of these prior medical conditions, we have conducted a large case-cohort study in Denmark that involves access to details of the conditions as contained in medical records. Ongoing analyses are assessing relationships of cancer risk according to details of the prior diagnoses.